Differential effect of Type I and Type II diabetes on antipyrine disposition in man

Zysset, Thomas; Wietholtz, H.

doi:10.1007/bf00542438

Cited by 33 publications

(38 citation statements)

References 26 publications

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“…Drug clearance was significantly increased in untreated patients of type 1 diabetes, which can be reversed by insulin treatment (Zysset and Wietholtz, 1988;Goldstein et al, 1990). This result was consistent with the observation in a streptozotocin-induced type 1 diabetic mouse model, in which the mice exhibited an increased Cyp2b10 basal expression that can be corrected by insulin treatment (Sakuma et al, 2001).…”

Section: Drug Metabolism Can Be Affected By Energy Metabolismsupporting

confidence: 78%

Pregnane X Receptor and Constitutive Androstane Receptor at the Crossroads of Drug Metabolism and Energy Metabolism

Gao¹,

Xie²

2010

Drug Metab Dispos

117

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ABSTRACT:The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are two closely related and liver-enriched nuclear hormone receptors originally defined as xenobiotic receptors. PXR and CAR regulate the transcription of drug-metabolizing enzymes and transporters, which are essential in protecting our bodies from the accumulation of harmful chemicals. An increasing body of evidence suggests that PXR and CAR also have an endobiotic function that impacts energy homeostasis through the regulation of glucose and lipids metabolism. Of note and in contrast, disruptions of energy homeostasis, such as those observed in obesity and diabetes, also have a major impact on drug metabolism. This review will focus on recent progress in our understanding of the integral role of PXR and CAR in drug metabolism and energy homeostasis.

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Section: Drug Metabolism Can Be Affected By Energy Metabolismsupporting

confidence: 78%

Pregnane X Receptor and Constitutive Androstane Receptor at the Crossroads of Drug Metabolism and Energy Metabolism

Gao¹,

Xie²

2010

Drug Metab Dispos

117

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“…In agreement with others (19,29), drug half-life and volume of distribution in the present study were significantly reduced in the presence of diabetes. Furthermore, total systemic clearance of cyclosporine was increased in the diabetic rat group, most likely due to induction in microsomal enzyme activity (29).…”

Section: Discussionsupporting

confidence: 81%

“…The half-life and volume of distribution of drugs primarily cleared by the hepatic microsomal system were markedly reduced in diabetics compared to normal controls (19). In contrast, the half-life of cyclosporine was significantly prolonged in early onset streptozocin-induced diabetic rats (20).…”

Section: Introductionmentioning

confidence: 91%

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Cyclosporine pharmacokinetics and effect in the Type I diabetic rat model

Brunner

Iyer

Vadiei

et al. 1989

Eur. J. Drug Metab. Pharmacokinet.

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Recent clinical studies have demonstrated the potential benefit of the T-cell-specific immunosuppressant, cyclosporine, in the treatment of Type I insulin-dependent diabetes. In the present study, steady-state cyclosporine pharmacokinetics, fasting glucose and insulin levels and renal function were examined in stable insulin-dependent diabetic rats and compared to non-diabetic rats. Mean creatinine clearance 30 days following diabetes induction was not significantly different from saline controls. Cyclosporine treatment (5 mg/kg/day i.v. for 13 days) did not significantly alter creatinine clearance in either group; however, renal function of vehicle-treated diabetic rats was markedly reduced compared to other groups. Serum insulin concentrations were significantly greater in diabetic rats treated with cyclosporine compared to the control group (35.1 +/- 22.7 vs. 16.0 +/- 8.1 microU/ml; P less than 0.05). Glucose levels were proportionately reduced in diabetic rats treated with cyclosporine. Area under the concentration-time curve, half-life and volume of distribution of cyclosporine were significantly reduced in diabetic rats compared to non-diabetic controls. In summary, the pharmacokinetics and pharmacodynamics of cyclosporine were significantly different in the insulin-dependent diabetic rat model compared to normal controls. Furthermore, short-term cyclosporine therapy reduced the extent of experimental diabetic nephropathy observed in this model.

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“…For example, the Vd of phenazone is increased (Salmela et al 1980), decreased (Zysset & Weitholtz 1988) or unchanged (Murali et al 1983;Narang et al 1987;Pirttiaho et al 1984;Zysset & Weitholtz 1988) by diabetes. As discussed in more detail below in the section dealing with the effects of diabetes on drug biotransformation, inconsistencies may arise because of inappropriate controls, the presence of undetected complications of diabetes and failure to distinguish between 100M and NIOOM.…”

Section: Distributionmentioning

confidence: 95%

The Effects of Diabetes Mellitus on Pharmacokinetics and Pharmacodynamics in Humans

Gwilt

Nahhas

Tracewell

1991

Clinical Pharmacokinetics

144

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The article reviews the effect of diabetes on the pharmacokinetics and pharmacodynamics of drugs in humans. For most drugs which cross the gastrointestinal wall by passive diffusion, oral absorption is unlikely to be affected by diabetes, although a delay in the absorption of tolazamide and a decrease in the extent of absorption of ampicillin have been reported. Subcutaneous absorption of insulin is more rapid in diabetic patients, whereas the intramuscular absorption of several drugs is slower. The binding of a number of drugs in the blood is reduced in diabetes, which may be due to glycosylation of plasma proteins or displacement by plasma free fatty acids, the level of which is increased in diabetic patients. Plasma concentrations of albumin and alpha 1-acid glycoprotein do not appear to be changed by the disease. The distribution of drugs with little or no binding in the blood is generally not altered, although the volume of distribution of phenazone (antipyrine) is reduced by 20% in insulin-dependent diabetes mellitus (IDDM). In contrast to animal studies, the metabolic clearance of most drugs in humans appears to be unaffected or slightly reduced by the disease. The presence of fatty liver in non-insulin-dependent diabetes mellitus (NIDDM) may contribute to a reduced hepatic clearance, whereas decreased binding in the blood may cause an increase in clearance. The effect of diabetes on hepatic blood flow in humans appears to be unknown. Diabetes affects kidney function in a significant number of diabetic patients. During the first 10 years after the onset of the disease, glomerular filtration is elevated in these patients. Thus, the renal clearance of a number of antibiotics has been shown to be increased in diabetic children. As the disease progresses, renal function is impaired and glomerular function declines from the initial elevated state. In diabetic adults the renal clearance of drugs either is comparable with that found in nondiabetic individuals or is reduced. A limited number of studies have been conducted comparing the dose-response of cardiovascular drugs in diabetic patients with that in nondiabetic controls. Decreased, increased and unchanged responses have been reported. It is apparent that in some cases an altered response may be observed for a drug when administered to a diabetic patient compared with a similar nondiabetic individual. At the present time, it is not possible to ascertain whether these studies reflect true pharmacodynamic changes or merely alterations in pharmacokinetics.(ABSTRACT TRUNCATED AT 400 WORDS)

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Differential effect of Type I and Type II diabetes on antipyrine disposition in man

Cited by 33 publications

References 26 publications

Pregnane X Receptor and Constitutive Androstane Receptor at the Crossroads of Drug Metabolism and Energy Metabolism

Pregnane X Receptor and Constitutive Androstane Receptor at the Crossroads of Drug Metabolism and Energy Metabolism

Cyclosporine pharmacokinetics and effect in the Type I diabetic rat model

The Effects of Diabetes Mellitus on Pharmacokinetics and Pharmacodynamics in Humans

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